**4. Action mechanisms of insecticides**

The nervous system of insects is developed and it has characteristics similar to the nervous system of mammals. Therefore, insecticides do not have species-specific selective effects, and all mammals, including humans, are extremely sensitive to the toxic effects of insecticides. Selective action between insects and mammals is usually the result of differences in detoxification mechanisms or differential interactions in their target structures. Insecticides cause more acute poisoning in non-target organisms compared to the other pesticides [8]. The effects of insecticides may vary depending on features such as their chemical formulations, amount and duration of application, temperature and pH of the environment etc. [13–15]. The continuous use of the same insecticide species in agricultural practices causes insect species to lose their sensitivity and become resistant to these insecticides over time. As a result, the need for continuous renewal has emerged due to the decreasing effectiveness of organophosphate, carbamate, organochlorine, and pyrethroid insecticides, and alternative new insecticides such as neonicotinoid insecticides have been developed [16, 17].

The majority of insecticides used today are neurotoxic substances and act by poisoning the nervous systems of target organisms [18, 19]. The action mechanism of organophosphate and carbamate insecticides is based on the inhibition of the acetylcholinesterase enzyme (AChE). Organophosphate insecticides or their active metabolites covalently bind to the hydroxyl group of serine in the active site of AChE with phosphate radicals and cause inhibition of the enzyme. Detoxification of organophosphates includes hydrolysis reaction catalyzed by A-esterases such as paraoxonase (PON) and stoichiometric binding reactions to B-esterases such as acetylcholinesterase, butyrylcholinesterase, and carboxylesterase in plasma [19–22]. Carbamate insecticides also involve "carbamylation" of the enzyme. The cholinergic syndrome that develops in acute poisonings caused by this group of insecticides is short-lived, since the enzyme's reactivation time is short after carbamylation [23]. Organochlorine insecticides are effective on the central nervous system and

*An Overview of the Biochemical and Histopathological Effects of Insecticides DOI: http://dx.doi.org/10.5772/intechopen.100401*


#### **Table 1.**

*Mechanisms and effects of neurotoxic insecticides in mammals [18].*

their action mechanism may vary according to the structure of the insecticide. DDT (Dichlorodiphenyltrichloroethane) changes the permeability of sodiumpotassium channels in the nerve membrane and causes excessive nerve stimulation by causing slow closure of sodium channels. In cyclodiene and lindane exposure, neurotransmitter release from synapses is affected. These compounds antagonize GABA (γ-aminobutyric acid) and cause depolarization and overstimulation in the postsynaptic membrane [23, 24]. Pyrethroid insecticides, on the other hand, change the properties of voltage-dependent sodium channels and cause prolonged opening of the channel. In this way, excessive excitation occurs in the central nervous system [18, 23]. **Table 1** shows the action mechanisms of insecticides [18]. In recent years, it has been reported that insecticides, in addition to these effects, increase the production of reactive oxygen species (ROS), thus causing an increase in oxidant molecules and a decrease in antioxidant molecules in the organism [5–7, 17, 19, 25, 26]. ROS formation rate and elimination work in balance. If it breaks down in favor of ROS, oxidative stress occurs. Due to oxidative stress, peroxidative damage to macromolecules and membranes of cells occurs in organisms. Moreover, their metabolic activities in cell components are impaired. Known to tissue and organ pathologies occur in the presence of oxidative stress in the organism [27–34].

### **5. Biochemical effects of insecticides**

Pesticides are metabolized in the liver by cytochrome P450 enzyme systems, passing through the human body through the skin, respiration, and digestion. Pesticides stimulate lipid peroxidation in hepatic microsomes and cause a decrease in cytochrome P450 enzymes, glucose 6-phosphatase and pyrophosphatase activities [35]. Detoxification of organophosphate pesticides, including organophosphate insecticides, is provided by A-esterases such as paraoxonase (PON) and B-esterases such as acetylcholinesterase, butyrylcholinesterase, and carboxylesterase in plasma [19, 20].

In a study conducted on agricultural laborers who were exposed to pesticides for a long time, it has been observed that protein levels significantly reduced and aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities significantly increased in these

people, compared to people who were not directly exposed to pesticides [36]. On the other hand, in a study conducted on pesticide sales people in the GAP Region, it was observed that AST and ALT activities increased, while ALP and LDH activities decreased in those who worked at pesticide sales locations for a long time [37].

In an experimental study in which the organophosphate insecticide diazinon was applied to rats for 4 weeks, it was reported that this insecticide caused significant changes in hematological and biochemical parameters. Accordingly, it was reported that serum biochemical parameters AST, ALT, ALP, LDH, creatine kinase (CK) activities, and urea, uric acid, and creatinine values of rats, to which diazinon was administered, significantly increased, compared to the control group [38]. It was reported that DDT administration to rats increased serum AST and ALT levels,


**Table 2.**

*The effects of insecticides on oxidative stress parameters in experimental animal models.*

#### *An Overview of the Biochemical and Histopathological Effects of Insecticides DOI: http://dx.doi.org/10.5772/intechopen.100401*

stimulated inflammation, and suppressed the immune system [39]. In another study conducted on rats with the carbamate insecticide carbofuran, it was observed that this insecticide increased cholesterol level and AST, ALT, LDH activities and decreased high-density lipoprotein (HDL) level and AChE activity in rat serum after 24-hour treatment [40]. In a study conducted on fish with the organochlorine insecticide lindane, it was reported that glucose increased and total protein decreased at low doses and increased at high doses [41]. In another study conducted on fish, it was stated that the pyrethroid insecticide deltamethrin increased the biochemical parameters cholesterol and glucose values and AST, ALT, ALP activities and decreased the total protein and albumin values [42].

Oxidative stress parameters are among the most important biochemical parameters affected by pesticides. Most environmental pollutants, including pesticides, have the ability to induce oxidative stress in almost all organisms, especially fish. Some studies with pesticide-treated fish revealed that pesticide treatment caused oxidative stress by increasing reactive oxygen species (ROS) in the cells and tissues of fish [43–45]. Oxidative stress negatively affects life of living creatures by causing genotoxic effects, lipid peroxidation and enzyme inhibitions. Lipid peroxidation, which occurs as a result of the toxic effects of pesticides, is an important indicator of oxidative stress and can be demonstrated by measuring malondialdehyde (MDA) levels [16, 46].

As in the other higher organisms, fish have important defense mechanisms to cope with oxidative stress. This defense mechanism, generally called as antioxidant, plays an important role in the survival of fish and in their adaptation to chemical stress. Antioxidant defense systems are composed of enzymatic components such as Paraoxonase (PON), superoxide dismutase (SOD), catalase (CAT), glutathione-Stransferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and non-enzymatic components such as glutathione (GSH). SOD and CAT are important antioxidant enzymes that form the first defense mechanism against pesticides. GSH is also an important non-enzymatic antioxidant molecule that protects cells against the harmful effects of oxidative stress [16, 19, 46, 47].

Insecticides that contaminate aquatic systems not only cause toxic effects on fish but also adversely affect living creatures at higher trophic levels through the food chain and cause many negative situations in humans and animals. Insecticides cause significant changes on oxidative stress parameters in humans and animals as well as in fish. **Table 2** shows the effects of insecticides on oxidative stress parameters in experimental animal models.
